I am skeptical about nutraceutical peptides targeting dipeptidyl peptidase-4 (DP-4) or angiotensin converting enzyme (ACE) for one simple reason: our intestines are good at absorbing dipeptides, but when it comes to tripeptides, they did it poorly. So I would not have a high hope for tripeptides or tetrapeptides.

Dipeptidyl peptidase IV (DPP-4) enzyme is responsible for the degradation of incretins that stimulates insulin secretion and hence inhibition of DPP-4 becomes an established approach for the treatment of type 2 diabetics. We studied the interaction between DPP-4 and its inhibitor drugs (sitagliptin 1, linagliptin 2, alogliptin 3, and teneligliptin 4) quantitatively by using fragment molecular orbital calculations at the RI-MP2/cc-pVDZ level to analyze the inhibitory activities of the drugs. Apart from having common interactions with key residues, inhibitors encompassing the DPP-4 active site extensively interact widely with the hydrophobic pocket by their hydrophobic inhibitor moieties. The cumulative hydrophobic interaction becomes stronger for these inhibitors and hence linagliptin and teneligliptin have larger interaction energies, and consequently higher inhibitory activities, than their alogliptin and sitagliptin counterparts. Though effective interaction for both 2 and 3 is at [Formula: see text] subsite, 2 has a stronger binding to this subsite interacting with Trp629 and Tyr547 than 3 does. The presence of triazolopiperazine and piperazine moiety in 1 and 4, respectively, provides the interaction to the S2 extensive subsite; however, the latter's superior inhibitory activity is not only due to a relatively tighter binding to the S2 extensive subsite, but also due to the interactions to the S1 subsite. The calculated hydrophobic interfragment interaction energies correlate well with the experimental binding affinities (KD) and inhibitory activities (IC50) of the DPP-4 inhibitors.

Entedhar Sarha : Please stop plagiarizing other people's published work and presenting it as your own on this and other websites.

Hi Henry, Sorry for late response. I am quite inclined to study this subject further. Recently I was presented a product from s. Korea where the none and deca peptides have been blended with some phyto actives with reasonable claims of diabetes on pilot scale . They claim that this increases insulin uptake receptors. I am trying to understand MoA from them, but at same time Keen to know if similar research and outcome has been seen elsewhere?